zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad pathway in apoptosis of p815 mastocytoma cells.
- Author:
Su Bog YEE
1
;
Soo Jin BAEK
;
Hwan Tae PARK
;
Seung Hun JEONG
;
Jin Hee JEONG
;
Tae Hyun KIM
;
Jong Min KIM
;
Byung Kap JEONG
;
Bong Soo PARK
;
Taeg Kyu KWON
;
Il YOON
;
Young Hyun YOO
Author Information
1. Department of Anatomy and Cell Biology (BK21 program), Dong-A University College of Medicine and Medical Science Research Center, Busan 602-714, Korea. yhyoo@dau.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
14-3-3 proteins;
benzyloxycarbonylvalyl- alanyl-aspartyl fluoromethyl ketone;
bcl-associated death protein;
caspase 6;
genistein;
mastocytoma
- MeSH:
bcl-Associated Death Protein/*metabolism;
*Signal Transduction/drug effects;
Mitochondria/drug effects;
Mice;
Mastocytoma;
Hydrocarbons, Fluorinated/*pharmacology;
Genistein/pharmacology;
Enzyme Inhibitors/*pharmacology;
Cell Line, Tumor;
Caspase 6/antagonists & inhibitors/*metabolism;
Benzyl Compounds/*pharmacology;
Apoptosis/*drug effects;
Animals;
Amino Acid Chloromethyl Ketones/pharmacology;
14-3-3 Proteins/*metabolism
- From:Experimental & Molecular Medicine
2006;38(6):634-642
- CountryRepublic of Korea
- Language:English
-
Abstract:
In a preliminary study, we found that benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD- fmk), unlike Boc-aspartyl(OMe)-fluoromethylketone (BocD-fmk), at usual dosage could not prevent genistein-induced apoptosis of p815 mastocytoma cells. This study was undertaken to reveal the mechanism underlying the incapability of zVAD-fmk in preventing this type of apoptosis. We observed that 14-3-3 protein level was reduced in genistein-treated cells and that BocD-fmk but not zVAD-fmk prevented the reduction of 14-3-3 protein level and the release of Bad from 14-3-3. We also demonstrated that truncated Bad to Bcl-xL interaction in genistein- treated cells was prevented by BocD-fmk but not by zVAD-fmk treatment. Our data indicate that BocD- fmk, compared to zVAD-fmk, has a certain preference for inhibiting 14-3-3/Bad signalling pathway. We also elucidated that this differential efficacy of BocD-fmk and zVAD-fmk resulted from the different effect in inhibiting caspase-6 and that co-treatment of zVAD-fmk and caspase-6 specific inhibitor substantially prevented genistein-induced apoptosis. Our data shows that caspase-6 plays a role on Bad/14-3-3 pathway in genistein-induced apoptosis of p815 cells, and that the usual dose of zVAD-fmk, in contrast to BocD-fmk, did not prevent caspase-6 acting on 14-3-3/Bad-mediated event.
